Diagnostic accuracy of plasma kynurenine/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis

Abstract

The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB. Method: We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV. Results: The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from À0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P < 0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P < 0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%. Conclusion:The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.

Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV)

“…Plasma K/T ratio showed a significant inverse correlation with BMI in TB patients but not in controls. The relation between K/T ratio and BMI in TB patients is consistent with our previous findings and those of others in nonpregnant populations [ 31 , 32 ]. As weight loss is a cardinal sign of TB, an appropriate TB biomarker should be expected to show inverse correlation with BMI in TB patients.…”

“…These findings, together with our previous work [ 17 , 32 ], suggest that plasma K/T ratio can be used to diagnose active TB disease in individuals with HIV, including pregnant women. We report here that elevated K/T ratio could detect almost all active TB cases among pregnant women.…”

Resistance of Mycobacterium tuberculosis to indole 4-carboxamides occurs through alterations in drug metabolism and tryptophan biosynthesis

“…This strategy, however, is not effective against Mtb and other bacteria capable of de novo L-Trp biosynthesis. Nevertheless, catabolism of L-Trp by IDO-1 was evident in plasma samples obtained from patients with either active or latent TB (Adu-Gyamfi et al, 2020;Collins et al, 2020), further implicating the importance of L-Trp biosynthesis in Mtb infection. Indeed, chemical inhibition of bacterial L-Trp biosynthesis was shown to synergize with the host-induced L-Trp starvation to afford Mtb killing in vivo (Zhang et al, 2013), demonstrating the feasibility of targeting this pathway for Mtb chemotherapy.…”

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

“…material). Further development of high-throughput analytical platforms including enzymatic methods [136] may hold promise for the clinical adoption of KP metabolites as biomarkers for monitoring of CKD.…”